The involvement of the partially reduced oxygen intermediates: the superoxide radical, hydrogen peroxide and the hydroxyl radical, in the toxic mechanism of acute cadmium poisoning (fume fever) will be investigated. Isolated pulmonary macrophages will be exposed to CdCl2 in a cell culture system. Parameters which will be measured include: cell viability, cell respiration, cell morphology, particle uptake, cellular levels of the antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, and intracellular distribution of cadmium. Isolated subcellular constituents will also be exposed in vitro to varying CdCl2 concentrations, and the affect of cadmium on their basal rates of oxygen metabolite formation will be monitored. This proposal is based on the hypothesis that the toxicity of fume fever is related mechanistically to the toxicity of oxygen. However, unlike exposure to hyperoxia where cellular damage arises from increased rates of generation of oxygen metabolites, the oxidative damage due to acute cadmium exposure may result from compromised 'antioxidant' enzyme levels. This specifically detailed study not only will contribute toward understanding the mechanism of acute cadmium toxicity, but also will develop a foundation for further studies with other pneumocytes. Data obtained should help to explain the differences in cell sensitivity to cadmium observed anatomically between lung cells. It also may aid in developing therapeutic measures for agents in general whose mechanism of cell damage is related to intracellular oxygen metabolite formation.